JPS59148724A - Paste for stopping bleeding and bridgeing loss temporarily in case of bone injury - Google Patents

Abstract

1. A paste for haemostasis and temporary bridging of defects in cases of bone trauma, characterized in that it contains from 3 to 60 % by weight of prolamin and from 5 to 20 % or tricalcium phosphate or hydroxyl apatite in finely dispersed form and a physiologically compatible diluent.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a paste for hemostasis in case of bone trauma and for temporary bridging of defects.

Bone wax was first reported by Horsley in 1892, and since then has undergone various improvements and has been used as a means to mechanically stop bone bleeding. Its initial composition was 7 parts beeswax, 1 part almond oil and 1 part salicylic acid.

The bone wax most frequently used today consists of 89 parts beeswax and 11 parts isopropyl palmitate. This preparation elicits a strong foreign body reaction and chronic inflammatory response. Even after 12 weeks, only a small portion of the bone is resorbed, which slows down bone regeneration. From a clinical point of view, pseudoarthro
ses) must be observed.

The object of the invention is a paste for hemostasis in case of bone trauma and temporary bridging of defects, which safely stops bleeding in traumatized bones and does not interfere with bone formation, but rather induces osteogenesis. The objective is to provide a paste that acts on the skin. The solution to the problem provided is that a paste containing prolamin, finely dispersed tricalcium phosphate or hydroxyapatite and a physiologically compatible diluent provides optimal hemostasis of traumatized bone and temporarily bridges defects. It is based on the surprising discovery that it is an excellent means of countermeasures.

The invention thus relates to the subject matter specified in the claims.

The diluent used is preferably a mixture of an aliphatic alcohol having 2 to 5 carbon atoms, in particular ethanol, and water in a volume ratio of the former to the latter of approximately 1:1 to 10:0.5.

Prolamin is the main protein component of grains or ground flour. Contrary to all other proteins, prolamins can be extracted from flour using 80% alcohol. Prolamins are not soluble in absolute alcohol or water. The most important prolamins are zttin, gliadin and hordein.
dein). Zein is preferred in the present invention. Prolamin preferably zein is added to the paste from 3 to 6
It is used in an amount of 0% by weight, preferably 5-45% by weight.

Contrary to all other proteins, prolamins are soluble in dilute alcohols and other solvents, but not in water. A mixture of ethanol and water is a suitable solvent and diluent. The water content ranges from 4 to 50 inches depending on the rate at which the prolamins are desired to precipitate. In ethanol, prolamins form a viscous, slightly chickentropic solution. The viscosity of the solution increases as the concentration of ethanol increases at the same prolamin content.

On the other hand, at a given concentration of ethanol, the viscosity increases as the concentration of prolamins increases.

Since prolamins are resorbable, no appreciable linear joints can develop as a result of the bone wax not being resorbed or resorbed slowly, as in the case of sternal closure, for example.

The finely dispersed hydroxyapatite or tricalcium phosphate content promotes bone regeneration. The particle size of hydroxyapatite or tricalcium phosphate is generally about 3 to 20 μm.
1, especially in the range of about 10 to 15 microns.

Methyl cellulose or carboxymethyl cellulose 2
Additions of ~10% by weight give optimal paste consistency, thus producing a formulation that is a thin film and is easily applied to stop bone bleeding. Similarly, large bone defects can be filled and bridged by applying paste. In addition, compound fractures (cotrtminutgd frac
It is also possible to repair trbres).

Antibiotics can be added to the paste for use in preventing or treating infections. Examples of useful antibiotics are tobramycin, gentamicin, cefotaxime (cg
fotαzim) and mixtures thereof. Antibiotics are used in amounts sufficient to completely inhibit the growth and kill the bacteria.

Instead of or in addition to antibiotics, cytostatic drugs can be included. Examples of cell growth inhibitors are midomycin, d
ichlo-rene), decarbacine (decar
bacin) or cisplatin
). The cytostatic agent is used in an amount sufficient to retard tumor growth.

When fine fibers of absorbable polymer are added in an amount of 1 to 15% by weight, the hardness of the paste changes so that it can be kneaded and molded, thereby temporarily bridging bone defects. It can be applied as a means to

Poly(lactide-glycolide) copolymers are hydrolyzable aliphatic polyesters used to make absorbable surgical suture materials. Other absorbent fiber polymers that may be incorporated into the pastes of the present invention are polyglycolides, polylactides, polyoxylates, polysuccinates, polydioxanones and poly(ester amides).

The paste can be made in the manner disclosed in US Pat. No. 4,268,495. From this US patent, Pro 2
An injectable solution containing ttmboli
zation) and occlusion (occlwsion).

It is easy to press the crosswireable paste into the bone defect and mold it to fit the desired shape.

Katamashi solidifies for about 30 to 90 minutes.

The paste can be sterilized by gamma radiation, heat, or the addition of about 0.25-0.5% by weight propylene oxide.

The invention will be explained by examples.

Example 1 Mix the paste from the ingredients below.

Ethanol 60 t v/v 51.71 Zein 19.4 g Methyl cellulose s, o g Tricalcium phosphate (particle size approx. 15.0 plOμm) Propylene oxide i, o 11 Zein in 60 t aqueous ethanol: Gatamashi Stir carefully. After completely dissolving (about 12-14 hours)
The pH was adjusted to about 6.5-6.8 using a physiologically compatible acid or base.

Methylcellulose and tricalcium phosphate were then introduced into the resulting viscous solution. The resulting paste was finally mixed with Ig propylene oxide under cooling and immediately bottled.

#1 fibers 1-131I of an absorbent polymer, preferably polyglycolide or polylactide, can also be added to the paste.

Example 2 A paste is prepared according to Example 1 with the following ingredients:

Ethanol 60% υ/v 51.71 Zein 19.4.9 Carboxymethyl cellulose 5oI hydroxyapatite (particle size approx. 10A??t) 20.0&
Propylene Oxide i,og The sternum is separated along its long axis and a drop of the base prepared in Examples 1 and 2 is applied to the spongy part of the bone to stop the bleeding. The paste can be applied well and penetrates smoothly into the pores of the bone.

Diffuse bleeding in the bone stops immediately.

Post-mortem examination 28 days later reveals partial bridging of the previous defect. It is no longer possible to prove hemostatic substances histologically.

Example 3 A paste is prepared according to Example 1 from the components listed below.

Engineering p/-le 60% v/v 51.71
1 Zein 19.4 g Methylcellulose 5. OI tricalcium phosphate (particle size approximately 10 μm) t5. oy tobramycin 0.7g propylene oxide 1. OgThis paste of the invention is used to fill holes in infected bones. Bone pores in chronically infected bone marrow serve as areas of reduced resistance for infection recurrence.
tiae) deroru. This paste is used to clear the bone marrow and stop any bleeding that may have started when the tissue is opened up for examination. At the same time, any holes are either completely filled or filled along the wall, depending on the size.

In bacteriological tests, bone fragments taken periodically during the experiment showed a clear inhibition of fungal growth over a period of 28 days, with a tendency to decline thereafter.

Example 4 According to Example 1, a paste is prepared from the following ingredients:

Ethanol 60%t+/V 51.7Ji
'Zein 19.4.9 Carboxymethylcellulose 5.0g Midomycin
0.8I propylene oxide
1. This paste of the present invention is used to retard the growth of certain or probable bone or bone marrow malignancies. Regarding the cytostatic midomycin, the paste can be applied both in flowable consistency and in the form of fine solid particles by precipitation or solvent evaporation.

A flowable form is chosen when it is desired that the paste stop bleeding from the tumor area. It is also possible to treat bone tumors that are known and thought to be inoperable, but which have already undergone surgery and require means to stop bleeding. Prophylactic introduction of a cytostatic agent at the border of the resection is highly beneficial, as it ensures that the effect of the cytostatic agent lasts sufficiently long. The range of effect is imagined to be about 1 cR away from the paste. Since the systemic effect in this case is conferred only under certain conditions, the release of the cytostatic agent can be very high. In fact, about 1.5 (
There is a lid extending to a distance of Mll (gamma). In this case, a second effect, that of cellular embolism, is added to the first desired hemostatic effect.

A solid paste is desirable if the bone area does not have to be completely blood-free.

Claims (1)

[Claims] Bone 11+ wound preparation, characterized in that it contains 1.3-60% by weight of prolamins, 5-20% by weight of tricalcium phosphate or hydroxyheptapatite in finely dispersed form and a physiologically compatible diluent. Paste for hemostasis and temporary bridging of defects in cases. 2. The prolamin is zein and the diluent is the return prime number 2.
A paste according to claim 1, comprising a mixture of -5 aliphatic alcohol and water. a p-2) d! A paste according to claim 1 or 2, containing 2 to 10% of methylcellulose or carboxymethylcellulose. 4. The paste according to any one of claims 1 to 3, wherein the paste further contains an antibiotic or a cell growth inhibitor. h. The paste contains fine fibers of an absorbent polymer, preferably polyglycolide, polylactide, poly(lactide-glycolide) copolymer, polyoxylate, polysuccinate, polydioxanone or poly(ester amide). The paste according to any one of Items 1 to 4. s, lip! Hemostasis in the case of bone trauma in humans or ljrgm, characterized in that the paste according to any one of claims 1 to 5 is applied in a sufficient amount to the traumatized area. A method for temporarily bridging defects.